These Ki-rasG12C transgenic mice express the human KRASG12C mutation under the control of a tetracycline-responsive promoter element (TRE; tetO). When hemizygotes are bred with another transgenic mouse expressing either reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA) under the regulation of tissue-specific promoters, transgene expression in the appropriate tissues of the bitransgenic offspring can be regulated with the tetracycline analog, doxycycline.
Mark S. Miller, Wake Forest Univ, School of Medicine
Hemizygous mice are viable and fertile. These Ki-rasG12C transgenic mice express the human KRASG12C mutation under the control of a tetracycline-responsive promoter element (TRE; tetO). When hemizygotes are bred with another transgenic mouse expressing either reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA) under the regulation of tissue-specific promoters, transgene expression in the appropriate tissues of the bitransgenic offspring can be regulated with the tetracycline analog, doxycycline.
When crossed with mice containing a lung-specific rtTA protein (e.g. Stock Nos. 006222, 006232, 006242 or 006225), treatment with doxycycline results in the formation of benign hyperplastic lesions starting at 12 weeks and the development of benign adenomas by 6 months. Tumors do not progress in size, but multiplicity increases upon further treatment with doxycyline. These bitransgenic mice live for at least 12 months and show a benign phenotype as compared with other mutant KRAS transgenic strains (e.g. Stock No. 004375), which demonstrate more aggressive tumor phenotypes. Doxycycline withdrawl from the diet of bitransgenic mice results in tumor regression.
A genomic segment including the KRASG12C (Ki-rasG12C) mutation was cloned from the H358 human lung bronchioalveolar cell line and placed under the regulation of a tetracycline-responsive element (TRE; tetO). The transgenic construct was microinjected into fertilized FVB/N mouse eggs. Transgenic founders were crossed with non-transgenic littermates to establish germline transmission.
|Expressed Gene||KRAS, KRAS proto-oncogene, GTPase, human|
|Site of Expression|
|Allele Name||transgene insertion 9.1, Mark Miller|
|Allele Type||Transgenic (Humanized sequence, Inducible, Inserted expressed sequence)|
|Gene Symbol and Name||Tg(tetO/CMV-KRAS*G12C)9.1Msmi, transgene insertion 9.1, Mark Miller|
|Promoter||CMV, cytomegalovirus, human|
|Promoter||tetO, tet operator,|
|Expressed Gene||KRAS, KRAS proto-oncogene, GTPase, human|
|Strain of Origin||FVB/NTac|
|Molecular Note||A genomic segment including the KRASG12C mutation was cloned from the H358 human lung bronchioalveolar cell line and placed under the regulation of a tetracycline-inducible (tetO)/cytomegalovirus (CMV) promoter. Copy number is estimated at 22.|
|Mutations Made By|| |
Mark Miller, Wake Forest Univ, School of Medicine
When maintaining a live colony, hemizygous mice may be bred together, to wildtype (non-carrier) mice from the colony or to FVB/NJ inbred mice (Stock No. 001800). The Donating Investigator's laboratory has attempted to breed the transgene to homozygosity - while crosses between the KRASG12C mice are viable, they have been unable to obtain homozygous mice.
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
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The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
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